Desmoid Tumor

NORD gratefully acknowledges Raphael Pollock, MD, PhD, Professor of Surgery, Director of Surgical Oncology, Chief of Surgical Services, The Ohio State University-The James, for assistance in the preparation of this report.

Synonyms of Desmoid Tumor

aggressive fibromatosis

deep fibromatosis

musculoaponeurotic fibromatosis

nonmetastasizing fibrosarcoma

Subdivisions of Desmoid Tumor

No subdivisions found

General Discussion

Summary

Desmoid tumor commonly develops in the fibrous (connective) tissue of the body that forms tendons and ligaments, usually in the arms, legs or midsection, and also in the head and neck. These tissues of the body connect, support, and surround other body parts and organs. The myofibroblast is the cell considered to be responsible for the development of desmoid tumor. Regardless of its scientific classification, a desmoid tumor can be invasive to surrounding tissues and difficult to control. Desmoid tumors can develop virtually at any body site. Superficial desmoids tend to be less aggressive than deep desmoids (abdominal, extra abdominal, mesenteric). These tumors look like dense scar tissue and just like scar tissue, they adhere tenaciously to surrounding structures and organs, and, thus they are commonly difficult to remove. Surgery has been the traditional main mode of therapy for desmoid tumors but up to 20-50% of these tumors recur after surgery.

Introduction

The Greek word "desmos" which means tendon or band like has been the origin of the term desmoid and was coined by Muller in 1838. Desmoid tumor is called an aggressive fibromatosis as it has similarities with a malignant (cancerous) tumor called fibrosarcoma. However, it is considered benign because it does not metastasize (spread) to other parts of the body.

Signs & Symptoms

Desmoid tumors typically affect tissue that is elastic and easily moved, a tumor may exist for a long time before being discovered, growing large and pushing aside surrounding tissue. While each child or adult may experience symptoms differently, the following are the most common symptoms of desmoid tumors. The symptoms of desmoid tumors vary greatly depending on size, location, and spread of the tumor. Some of the common symptoms include the following:

A painless swelling or lump

Pain or soreness caused by compressed nerves or muscles.

Pain and obstruction of the bowels

Limping or other difficulty using the legs, feet, arms or hands or other affected part of the body.

Causes

The exact cause of desmoid tumor still remains unknown. Desmoid tumors may present sporadically or as a manifestation of a hereditary syndrome called familial adenomatous polyposis (FAP). FAP is a familial cancer predisposition syndrome which, if left untreated at an early age, almost always results in colorectal cancer. Up to 32% of FAP patients will develop desmoid tumors in their lifetime. These desmoid tumors are the result of mutations, or changes, in a gene called adenomatous polyposis coli (APC).

For most affected individuals, desmoid tumors occur in a sporadic manner, meaning that they are not caused by a predisposing genetic disease. People who develop desmoid tumors in a sporadic manner have no other health problems associated with mutations in the APC gene and have no close family members with the tumors. Repeated irritation or trauma to a certain part of the body, including surgical trauma, has been theorized to increase the risk of desmoid tumor occurrence. Estrogen also seems to play a role in the development of desmoid tumors.

Affected Populations

Desmoid tumors are reported to constitute 0.03% of all cancers. When present in individuals with FAP, the prevalence of desmoid tumors is as high as 13%. The estimated incidence in the general population is 2-4 per million people per year. Desmoid tumors are observed to be more common in persons aged 10-40 years than in others but do also occur in young children and older adults. Desmoid tumors most commonly occur in women after childbirth and the gender ratio is 2:1 for females to males. In children, the incidence is the same in both genders.

Related Disorders

Gardner’s syndrome is inherited in an autosomal dominant manner and is considered to be one subtype of FAP. It is a genetic disorder characterized by the presence of multiple polyps in the colon together with tumors outside the colon. The extracolonic tumors may include osteomas of the skull, thyroid cancer, epidermoid cysts, fibromas and sebaceous cysts. The countless polyps in the colon predispose to the development of colon cancer. Gardner’s syndrome is now known to be caused by mutation in the APC gene located in chromosome 5q21 (band q21 on chromosome 5, the same mutation as in all FAP disorders). Once regarded as a separate entity, following the characterization of the APC gene, Gardner’s has now been recategorized as a phenotypic variation of FAP. Typically, one parent has Gardner’s syndrome. Each of their children, male and female alike, are at 50% risk of inheriting the gene for Gardner’s syndrome and manifesting it.

Dermatofibrosarcoma is a cutaneous malignancy that arises from the dermis and invades deeper subcutaneous tissue such as fat tissue, fascia, muscle and bone. Currently, the cause of dermatofibrosarcoma is unknown. Laboratory studies have shown that chromosomal aberrations may contribute to the pathogenesis of dermatofibrosarcoma, especially a chromosomal translocation t(17;22) that fuses the collagen gene (COL1A1) with the platelet-deprived growth factor gene ; however, no evidence of hereditary or familial predisposition exists. In 10-20% of patients with this tumor, trauma at the site seems to be incriminated. Surgical and old burn scars and sites of vaccinations have all been reported as sites of dermatofibrosarcoma. Dermatofibrosarcoma is known to be a slow growing tumor. Because of the slow progression and because it starts as a small asymptomatic papule, the diagnosis is often delayed. The tumor may gradually enlarge into a lumpy nodule, or it may evolve into an atrophic and/or sclerotic plaque.

Fibrosarcomas are malignant tumors derived from fibrous connective tissue and characterized by immature proliferating fibroblasts or undifferentiated anaplastic spindle cells. A fibrosarcoma is a malignant (cancerous) tumor that originates in the connective fibrous tissue found at the ends of bones of the arm or legs, and then spreads to other surrounding soft tissues. Soft tissues include fat, muscles tendons (bands of fiber that connect bones to muscle) nerves, joint tissue, blood vessels and other fibrous tissue. It most commonly affects either a lower leg or arm.

There are generally two forms of this disease characterized by age of presentation. Infantile or congenital fibrosarcoma is the most common soft tissue sarcoma found in children less than one year of age. It presents as a rapidly growing mass at birth or shortly after. This form of fibrosarcoma is usually slow-growing, and tends to be more benign than fibrosarcoma in older children, which behaves more like the type found in adults. Adult form fibrosarcoma can occur in older children and in adolescents, roughly between the ages of 10 and 15. It is more aggressive than the infantile form and generally involves more complex treatment.

Though the exact cause of fibrosarcoma and other soft tissue tumors is not entirely understood, studies have suggested that this may be a hereditary syndrome. Researchers have identified a small number of families that contain several members from one generation who have developed soft tissue sarcomas. In addition, limited studies have shown a possible link between soft tissue sarcomas and the development of other types of cancer. A chromosomal rearrangement has been found in some fibrosarcomas.

Diagnosis

The most conclusive diagnostic procedure for desmoid tumor is a biopsy (a tissue sample from the tumor taken through a simple surgical procedure). A biopsy is the most important diagnostic test for this tumor. Electron microscopy may be performed in addition to the biopsy for obtaining further clarity and confirmation for the diagnosis. On electron microscopic examination, the spindle cells of desmoid tumors appear to be myofibroblasts. This finding is thought to represent an abnormal proliferation of myofibroblasts, which normally disappear gradually during the later stages of wound healing. Additionally, immunohistochemical stains can be done looking for nuclear accumulation of beta-catenin, a protein that is affected by the genetic mutations often found in desmoid tumors. Nuclear reactivity shows relatively high specificity, detected in up to 90% of desmoids, regardless of site. Finally, antibodies are often examined in desmoid tumors, including smooth muscle actin, desmin and KIT, to aid in distinguishing them from other tumors.

Standard Therapies

Treatment

Depending on the extent of the tumor growth and the overall condition of the patient the following treatment options are utilized.

Because desmoid tumor never metastasizes, surgery alone is often the only treatment and hence surgical removal of the tumor is the primary treatment. The recurrence rate for a desmoid tumor is often as high as 50% and hence more than one surgery is commonly needed. The tumor tends to become more aggressive when it recurs after resection. For patients who refuse surgery, are not appropriate candidates for surgery, or have recurrences not responding to repeated surgeries, the following options may be considered:

Radiation therapy may be used as a treatment of recurrent disease or as primary therapy to avoid mutilating surgical resection by using high-energy rays (radiation) from a specialized machine to damage or kill cancer cells and shrink tumors.

Anti-inflammatory medication may be given to help manage pain and swelling. In some cases these medications will cause the tumor to slowly shrink. Non-steroidal anti-inflammatory drugs (NSAIDs) and drugs such as Imatinib are being used by physicians to treat desmoid tumors. Imatinib has been shown to effectively treat desmoid tumors that cannot be safely removed via surgical means.

Hormone therapy – Because some hormones seem to increase the growth of desmoid tumors, anti-hormonal medications such as anti-estrogens and prostaglandin inhibitors may also be used in the pharmacologic therapy.

Chemotherapy – If surgeons are unable to remove the tumor because of the size or location as in the case of recurrent extra-abdominal desmoid tumors in which surgery is contraindicated, some types of chemotherapy are used to reduce tumor size. Some of the agents known to inhibit cell growth proliferation are Doxorubicin (Adriamycin, Rubex), Dacarabazine (DTIC-Dome) and Carboplatin (Paraplatin).

Monitoring – After surgery, MRI may be useful for monitoring recurrence. Positron emission tomography Scans (PET) is also growing in popularity for monitoring the recurrence of desmoid tumors as it is a noninvasive imaging technique that creates three-dimensional images of the heart, brain and other organs of the body.

Novel molecular-targeted therapies: Kinases are regulators of cell growth, differentiation, and motility. Because these processes are deregulated in tumors cells, a new class of drugs called receptor kinase inhibitors has been developed. Gleevec and Sorafenib are two kinase inhibitors that are being used in the treatment of desmoid tumors.

Watchful waiting policy: Because desmoid tumors do not metastasize and can be followed closely for growth and because treatment with surgery and/or RT and chemotherapy can cause significant morbidity and even mortality, patients with asymptomatic or minimally symptomatic disease and with stable appearance on screening modalities may appropriately be treated with a period of watchful waiting.

Investigational Therapies

Angiogenesis inhibitors: Newer substances that may be able to prevent the growth of tumors by blocking the formation of new blood vessels that feed the tumors are being currently investigated.

Chemotherapy agents: Researchers are also testing several chemotherapy drugs, or combination of drugs, that could prove to be most effective in treating desmoid tumors to avoid radical management via surgery.

Mutations in the gene for beta-catenin have been found to commonly occur in desmoid tumor. Mutation analysis may soon be used to predict the risk of recurrence and to aid in the design of individual therapies.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

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